Response: Among US women, a positive association between Pap test uptake and HPV vaccination has been shown, though potential variation of the association by race/ethnicity had not been explored previously. The prevalence of some HPV types varies across different racial/ethnic groups so it is important to explore the association between Pap test uptake and HPV vaccination in detail.

MedicalResearch: What are the main findings?

Response:Pap test uptake was significantly lower among those who had not initiated HPV vaccination (81.0%) compared to women who had initiated vaccination (90.5%) (adjusted prevalence ratio = 0.93, 95% CI: 0.90–0.96). This result was seen across most of the sociodemographic factors examined, though not statistically significant for non-Hispanic blacks, Hispanics, those with lower levels of education, or those with higher levels of income.

Medical Research: What is the background for this study? What are the main findings?

Response: Two vaccines against human papillomavirus (HPV) were licensed almost one decade ago. Since then multiple countries have implemented HPV vaccination programs to help reduce genital warts (one of the kinds of warts most harmful to people), but many struggle with low coverage rates. An important barrier to vaccination is the cost of the vaccines and less developed countries also face considerable logistical challenges. Both vaccines were administered as three dose schedules, but in early 2014 the WHO’s Strategic Advisory Group of Experts and the European Medicines Agency reviewed the evidence of reduced dose schedules of HPV vaccination, and subsequently recommended a two dose schedule for young girls. A reduction of the number of doses has obvious advantages; it would lower the costs, ease implementation of vaccination schedules and potentially increase coverage rates. Based on these recommendations, countries around the world have reduced the dosing schedule in their HPV vaccination programs for young girls to two doses. However, the current evidence is based primarily on immunological studies, and because the immune correlate of protection is not known, studies with disease endpoints are very important.

Using the biologically relevant endpoint of genital warts, this study aimed to assess the clinical effectiveness of a two dose schedule of quadrivalent HPV vaccine compared with the standard three-dose regimen administered at month 0, 2 and 6. We found that with the standard vaccination schedule, completion of the three dose regimen is important to gain maximal protection. However, the effectiveness of two doses increased significantly with increasing time between the doses, and with an interval of approximately 6 months between dose one and two, no differences could be found between two and three doses.

MedicalResearch.com Interview with:Dr. Johannes BerkhofDepartment of Epidemiology and Biostatistics, VU University Medical Centre
Amsterdam
Centre for Infectious Disease Control,
National Institute for Public Health and the Environment, Bilthoven, Netherlands

Medical Research: What is the background for this study? What are the main findings?

Response: Vaccination against the sexually transmitted human papillomavirus (HPV) is offered free-of-charge to 12-year-old girls in the Netherlands.
There is strong evidence that HPV also causes cancer in men: the virus is associated with cancers of the penis, anus, and oropharynx, and possibly with a small proportion of oral cancers. A number of these cancers will be prevented because vaccination of girls leads to a decrease of HPV in the general population and thus provides indirect protection to heterosexual men.

However, vaccine uptake among girls is only about 60 percent in the Netherlands. Moreover, men who have sex with men are at increased risk of HPV-related cancer and will not be protected by vaccination of girls.

On the basis of data from several epidemiological studies and a dynamic model for virus transmission, we calculated that, if the vaccine uptake is low, about 200 girls need to be vaccinated to prevent one case of cervical cancer and 470 boys need to be vaccinated to prevent one case of cancer in men.

An increase in vaccine uptake in girls will decrease the HPV infection risk in heterosexual men and if the uptake in girls is 60 percent, around 800 boys need to be vaccinated to prevent one additional case of cancer in men.

Medical Research: What is the background for this study? What are the main findings?

Response: In this sample of young women, vaccination was effective at reducing prevalence of vaccine-type HPV (6,11,16,18) compared to women who were unvaccinated. We also found a dose response, with young women who received at least 2 doses of the 3 dose vaccine series having a lower rate of vaccine-type HPV compared to those who only received one dose (8.6% compared to 16.9%, respectively).

Medical Research: What is the background for this study? What are the main findings?

Dr. Siu: Our study is a collaboration between researchers at the Princess Margaret Cancer Centre and the Canadian Center for Applied Research in Cancer Control. The study involves a statistical model being applied to a hypothetical population of 192,940 Canadian boys who were 12 years old in 2012, to determine the cost effectiveness of HPV vaccination for the prevention of oropharyngeal cancer. On the basis of this model, HPV vaccination for boys aged 12 years appears to be a cost-effective strategy for the prevention of oropharyngeal cancer in Canada. There are limitations to our study as it is based on statistical modelling with many assumptions. For instance, we could not easily address the impact of herd immunity which refers to the indirect protective effect offered by HPV vaccination in women.

Based on our statistical model, despite its limitations, the vaccine can potentially save $8 to $28 million CAD for a theoretical group of 192,940 Canadian 12-year old boys in 2012 over their lifetime. As stated, this is based on a theoretical model and not a randomized study, the results are relevant especially that HPV-related oropharyngeal cancer is increasing in incidence and HPV is surpassing smoking as a risk factor for this cancer in many developed countries.

Currently, the National Advisory Committee on Immunization (NACI) of the Public Health Agency of Canada recommends HPV vaccination of females 9 through 26 years of age to prevent cervical, vulvar, vaginal and anal cancers, and for anogenital warts; and of males 9 through 26 years of age to prevent anal canal cancers and their precursors, and for anogenital warts. However, funding is also provided for HPV vaccination in young females and not in young males.

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Squiquera: Ranpirnase is a small peptide that has a characteristic enzymatic activity against double stranded RNA (dsRNA). As a drug it has been extensively tested intravenously in high concentration for oncology in over 1000 patients with different types of malignancy, especially mesothelioma, with minimal side effects and mainly a transient increase of serum creatinine level observed.

In the last year we started a comprehensive antiviral program and obtained encouraging results in several RNA and DNA virus families. Several research groups have already studied the anti HIV activity. HPV was one of many viruses that showed a high selectivity index in our antiviral screening (the relationship between efficacy and cytotoxicity). We were encouraged by the low concentrations (nanomolar range) needed to stop virus reproduction in cell cultures. We performed in vitro analysis of two of the main HPV types that cause human disease (HPV 11 and 16). HPV 11 was highly sensitive to ranpirnase; and since this is one of the main virus type responsible for inducing genital warts, we decided to focus our efforts in bringing the drug to a new route of administration.

We set out to obtain and did obtain a formulation that was extremely stable, even at high temperatures. Before using it in patients, we performed testing for irritation using standardized Draize animal models. Even though we ran these tests in high concentrations (1 mg/ml) the final product was not irritant and was deemed safe to use in a clinical setting.

With these safety data on hand – plus extensive experience in IV dosing and non-irritation in animal models – we decided to make the formulation available as a compassionate use for patients with genital warts.

As we reported in our presentation in San Francisco, all cases that completed an 8-week treatment showed clearance of the lesions. Some of the cases were cleared in as soon as two weeks and the average time for clearance was 33 days. One of the patients had to be discontinued due to an eczematous skin reaction. We will be studying the characteristic of this effect in our trials. Continue reading →

Dr. Ryser: Infection with the human papillomavirus (HPV) is responsible for approximately 5% of all cancers worldwide. In addition to cervical cancers, HPV is associated with various other female and male cancers, including cancers of the anus and oropharynx. Despite expansive screening and vaccination programs, HPV-related cancers remain a serious public health concern in the US and abroad. To further improve public health interventions against HPV, a thorough understanding of the underlying biology is critical.

The lifetime risk of getting infected with HPV is as high as 80%, yet most individuals remain asymptomatic and clear the virus after 1-2 years. However, if an infection with a high-risk type of HPV persists, the virus can interfere with the replication mechanism of the host cells, and initiate tumor growth. Even though our understanding is incomplete to date, clearance of HPV infections is primarily attributed to an effective immune response.

Interestingly, recent studies about the stem cell dynamics in epithelial tissues – the types of tissues that are affected by HPV – have shown that the fate of these stem cells is random: most of the time, a stem cell divides into a new stem cell and a differentiating daughter cell; however, every now and then, a stem cell divides either into two stem cells, or into two differentiating daughter cells. These dynamics have not been acknowledged by the HPV community, and our goal was to develop mathematical models to examine whether the random division patterns of stem cells could play a role in the clearance of HPV infections.Continue reading →

Medical Research: What is the background for this study? What are the main findings?

Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions. Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs.

In countries with high female vaccination coverage (<50%), our main findings indicate:

sharp declines in HPV-related outcomes among females targeted for vaccination (e.g., HPV-16/18 infection and anogenital warts declined by more than 60% in females younger than 20 years), and

evidence of cross-protection with significant reductions in HPV-31/33/45 infection among females younger than 20 years

evidence of herd effects (indirect benefit of vaccination among unvaccinated individuals) with significant reductions in anogenital warts among males and older females.

In countries with low coverage (<50%), we report:

significant reductions in HPV-16/18 infection and anogenital warts among young females, with no indication of herd effects or cross-protection. Continue reading →

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Struyf: Cervical cancer is the fourth most common cancer among women, with estimates from 2012 indicating that there are 528,000 new cases and 266,000 deaths each year worldwide, the majority of cases occurring in developing countries (reference: Globocan 2012 at http://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp). Persistent infection with oncogenic human papillomavirus (HPV) is a necessary condition for the development of invasive cervical cancer. HPV type 16 (HPV-16) and HPV-18 are found in approximately 70% of cases. We conducted the Papilloma Trial Against Cancer in Young Adults (PATRICIA), a multinational clinical trial in 14 countries in Europe, the Asia-Pacific region, North America, and Latin America and enrolled over 18,000 women. The trial showed that the HPV-16/18 AS04-adjuvanted vaccine not only prevented persistent infections and high-grade cervical lesions associated with HPV types 16 and/or 18 included in the vaccine, but also protected against some common related oncogenic HPV types not included in the vaccine. However, during the analysis of this trial, we also noticed that for some rare nonvaccine oncogenic HPV types, the vaccine efficacy against infections did not seem to match the efficacy against lesions associated with the same HPV type. To investigate this, we re-analyzed the samples from the trial using a different PCR method and found that the HPV PCR methodology used per protocol may have underestimated the efficacy for non-vaccine HPV types in cases of multiple infections. While these results do not replace the results generated according to the study protocol and included in the product label, they are reassuring, as they confirm the cross-protective efficacy of the HPV-16/18 vaccine against some HPV types related to those included in the vaccine.Continue reading →

Dr. Joura: This study demonstrates that the new ninevalent HPV vaccine induces a good immunogenicity against HPV 6/11/16/18 and gives a 97% protection against disease caused by HPV 31/33/45/52/58. This has a potential of a 90% reduction of cervical cancer and other HPV related cancers and a similar protection against genital warts. The full benefit is seen in persons without current HPV infection, this reinforces early vaccination against HPV. The safety profile was favourable.Continue reading →

Response: After the widespread introduction of HPV vaccination of adolescent girls, a number of safety concerns have emerged. In this case, demyelinating diseases, including multiple sclerosis, occurring after HPV vaccination has been reported in social media, news media and medical journals.

Medical Research: What are the main findings?

Response: In a study of almost 4 million Danish and Swedish women, we found no support for an increased risk of multiple sclerosis or other demyelinating diseases following HPV vaccination. Continue reading →

Medical Research: What is the background for this study? What are the main findings?

Response: Anogenital human papillomavirus (HPV) infection and anal cancer are common among men who have sex with men (MSM) and preventable with the HPV vaccine. However, the optimal strategy for vaccinating MSM against HPV requires an accurate understanding of the age specific incidence of early HPV infection. In addition to understanding the optimal age at which to vaccinate young MSM, policy makers also need to know the vaccine coverage required in MSM. In this paper we aimed to provide estimates for the site specific incidence of HPV and to use this to estimate the probability of transmission per partner in a cohort of very young MSM aged 16 to 20 years. These data will assist governments in deciding what HPV vaccination strategy is likely to be the most effective in MSM.

Medical Research: What is the background for this study? What are the main findings?

Dr. Moro: Gardasil® is a human papillomavirus (HPV) vaccine recommended for all girls and boys at age 11 or 12, and teens and young adults who did not get the vaccine when they were younger. Because there is limited safety data available on use of the vaccine during pregnancy, it is not currently recommended for pregnant women. However, some pregnant women will inadvertently receive Gardasil® because they do not yet know that they are pregnant at the time of vaccination.

The study reviewed non-manufacturer reports to the Vaccine Adverse Event Reporting System (VAERS) about pregnant women who received Gardasil®. VAERS is a national vaccine safety surveillance program co-administered by the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA). VAERS accepts reports of health problems that occur after any US-licensed vaccine (these are called adverse events). VAERS may also accept reports not describing any health problem but vaccination errors (for example, administration of a vaccine not recommended to a particular group of people like pregnant women). VAERS is an early-warning system and cannot generally assess if a vaccine caused an adverse event.

After reviewing all non-manufacturer reports of Gardasil vaccination during pregnancy, this study found no unexpected patterns of safety issues for pregnant woman who received Gardasil®, or for their babies. This finding is reassuring and reconfirms the safety of this vaccine for pregnant women, as was previously reported by the pregnancy registry maintained by Gardasil®’s manufacturer.

Medical Research: What is the background for this study? What are the main findings?

Dr. Smith: The human papillomavirus (HPV) vaccine protects against types of HPV that cause cervical cancer and anogenital warts. The vaccine first became available in 2006. Since then, it has faced a great deal of controversy surrounding, in part, some of the unanswered questions about the real-world effects of the vaccine, especially on the young girls targeted for immunization. One issue that has received a great deal of public attention has been the concern that HPV vaccination might give girls a false sense of protection against all sexually transmitted infections that might lead them to be more sexually active than they would otherwise. As a result, some parents have been reluctant to have their daughters vaccinated. It is also reason why some religious groups have spoken out against the vaccine. This question is further important from a public health perspective because increases in risky sexual behaviour would inevitably also lead to increases in teen pregnancy and sexually transmitted infections (excluding anogenital warts), which would of course undermine the potential health benefits of the vaccine.

In this study, we directly addressed the question of whether HPV vaccination has led to increases in pregnancy and non-HPV-related sexually transmitted infections (both of which are proxies for risky sexual behaviour) among adolescent girls.

In our study of over 260,000 girls, we did not find any evidence that the HPV vaccine had a negative impact on these outcomes.

Medical Research: What is the background for this study? What are the main findings?

Dr. Qualls-Hampton: There are currently two vaccines approved by the Food and Drug Administration (FDA)—Gardasil for males and Gardasil and Cervix for females – that protect against the human papilloma virus (HPV). These vaccines are recommended by the ACIP for females ages 9 to 26 years and males ages 9 to 21 years. Both vaccines protect males and females against some of the most common types of HPV. HPV vaccines are administered in three doses over six months and are considered safe and effective. However, the promise of these vaccines is going unfulfilled as initiation and completion rates for the three doses are suboptimal among females and males.

Nationally, although HPV vaccination initiation coverage is increasing, overall vaccine completion rates are at suboptimal levels and below the U.S. Department of Health and Human Services’ Healthy People 2020 initiative target of 80%. Thus, many states are turning to legislative interventions in efforts to increase initiation and completion rates. This study examines HPV vaccination legislative initiatives and their impact, specifically in estimating state legislation’s effects on HPV vaccine initiation, completion and patient care provider recommendations by gender.

Medical Research: What should clinicians and patients take away from your report?

Dr. Franco: Our findings of oral transmission of human papillomavirus (HPV) infection in men are part of a larger molecular epidemiologic study called ‘HPV Infection and Transmission among Couples through Heterosexual Activity’ (HITCH) cohort study. The focus of the HITCH study is to understand how HPV is transmitted within couples via sexual contact and other behaviors. We measure the presence of this virus using highly-sensitive molecular assays for HPV DNA in the genital surfaces (vagina and penis), oral cavity, and hands. We also take a blood sample to look for the presence of antibodies against HPV. We take multiple samples over a period of two years at pre-scheduled visits. We have previously published results focused exclusively on genital transmission. The present report is the first in the HITCH study to look at what happens in terms of characteristics that place male participants to be at risk of oral HPV infection.

To our knowledge, this is the first study to show a high risk of oral HPV infection among men whose female partners had a genital or oral HPV infection, suggesting that transmission may occur through oral or genital routes. We looked at transmission for 36 individual HPV genotypes, which improved our ability to study risk determinants. Risk was also significantly higher among men who had ever smoked, had a high number of lifetime sex partners, or were in non-monogamous relationships. Our results are largely consistent with previous studies that have found male sex practices and smoking to be the most significant risk factors for oral HPV infection.Continue reading →

Dr. Schabath: Overall, the results from these analyses demonstrated that men who consumed the highest amounts of alcohol were associated with an increased risk for genital human papillomavirus (HPV) infections.

Dr. Pathak: Cervical testing for human papillomavirus (HPV) is being piloted as a more accurate method for cervical cancer screening than current cytology-based (“Pap smears”). However, cervical testing still requires gynaecological examination and a doctor or nurse to take the sample. This could be a deterrent to attending screening as it is invasive and time-consuming. Urine-based HPV testing would be a less invasive and more convenient alternative.

Our study was completed at the Queen Mary University London Women’s Health Research Unit. We pooled the results of 14 studies from around the world which tested 1443 women for HPV in urine and cervical samples. We found that detection of HPV in urine seems to have good accuracy for the detection of HPV present in the cervix. We also found that using first void samples (the first part of the stream of urine) was twenty-two times more accurate than random or midstream urine samples.

Dr. Hinrichs:Objective tumor regression occurred in 3/9 patients with metastatic cervical cancer. Two responses were complete and are ongoing 22 and 15 months after treatment with a single infusion of T cells targeting the HPV oncoproteins.Continue reading →

Dr. Smith: This study first demonstrated in vitro suppression of HPV expression. After a single dose at 24 hours and with repeated dosing every 24 hours for 7 days followed by 7 days of no treatment, HPV eradication was achieved. These findings were confirmed with in vivo animal studies. HPV expression was eradicated with once daily AHCC dosing for 90 days and sustained after 30 day observation off treatment. Immune modulation (increase) of IFNα (p < 0.03), IFNβ (p <0.03), and IFN (p< 0.03) and IgG1 (P < 0.05) was observed in AHCC treated mice compared to untreated controls.

AHCC mechanism of immune modulation of the IFN pathways to eradicate HPV was particularly relevant because E6/E7 oncogenic activity in HPV infection is believed to be related to suppression of IFN expression/signaling. These data suggest AHCC may help clear HPV infections and have a potential role in the prevention of HPV-related cancers.

Dr. Sacks: 2247 anonymous questionnaires were completed by young women, aged 13-19 years old, attending sexual health services across England, looking at their HPV vaccination outcomes and prevalence of risk factors associated with HPV acquisition and cervical cancer development, and comparing the survey results with national data where available. Known HPV acquisition and cervical cancer development risk factors include cigarette smoking, early age at first intercourse, increasing number of lifetime partners, co-infection with other sexually transmitted infections.

MedicalResearch.com: What are the main findings of the study

Dr. Sacks:

Young women, aged 13 to 19 years old attending sexual health services across England had higher prevalence of known risk factors associated with HPV acquisition and cervical cancer development, compared with national data.

Subgroups within the survey respondents were identified as having a significantly lower offer and significantly lower completion rate of the HPV vaccination. These subgroups included respondents from London, those of non-white ethnicities, 17 to 19 year olds, smokers and those not in education, employment or training (NEETs).

The highest risk individuals, in terms of HPV related risk factors, were the least likely to be offered and additional the least likely to complete the HPV vaccination course.

Currently sexual health services in England are not involved in the delivery of the HPV vaccination programme and this is felt to be a huge missed opportunity for the primary prevention of HPV acquisition and its potential sequelae. Sexual health services should be included as a supplementary HPV vaccination delivery site in order to target these particularly vulnerable young women and to increase the success of the HPV vaccination programme in England.

1. We conducted a case-control study in which we retrieved the HPV vaccination histories of young Australian women who were notified to the Pap smear registry with high-grade cervical lesions or with other types of cervical lesions, and compared them with the vaccination histories of women whose Pap smears showed only normal cytology.

2. We found that women with high grade cervical lesions were significantly less likely than women with normal cytology to have received 3 doses of the quadrivalent HPV vaccine, equivalent to a vaccine effectiveness of 46%.

3. The vaccine effectiveness among 15-19 year old women was even higher at 57%. We believe this reflects the fact that HPV16 causes an even higher proportion of high grade disease in young women due to its higher oncogenicity and shorter latent period.

4. The HPV vaccine had 34% effectiveness against other cervical lesions (i.e. those not proven to be high grade lesions on histology).

5. We also observed that 2 doses of the vaccine were 21% effective in preventing both high grade lesions and other grade lesions.Continue reading →

Dr. Meyers: The human papillomavirus type 16 (HPV16) is the most common HPV type associated with human cancer. It has always been assumed that HPV16 was susceptible to commonly used disinfectants. However, this has never been tested. We developed the only reproducible method to grow authentic HPV in the laboratory. Our studies show that highly resistant virus; more so than other non-enveloped viruses previously tested. Simply stated that any materials in a healthcare facility that rely on disinfectants (those presently used by healthcare facilities) do absolutely nothing to HPV. This suggests the possibility of risk of infection from inanimate objects, particularly those use in healthcare and dental clinics that depend on disinfectant treatment. Additionally it has been reported that at any one time 20% of individuals with anogenital HPV infections have the virus on their fingertips and the common hand sanitizers do nothing to inactivate the virus.Continue reading →

Answer: The main finding, when studying HPV vaccine effectiveness against condyloma by dose level is that 3 doses offered the maximum protection, although 2 doses also offered a substantial protection.Continue reading →

Dr. Schabath: In this study we found that Asian/Pacific Islander men had the lowest incidence of human papillomavirus (HPV) infection and that they exhibited a lower probability of acquiring new HPV infections. Furthermore, men of multiple and mixed race had the second lowest incidence of HPV infection and however, while they had a lower probability of acquiring HPV, they also had a lower probability of clearing an HPV infection once acquired.Continue reading →

Newswise — NEW YORK CITY (April 12, 2012) — Anal cancer is on the rise among HIV-positive women, according to a Montefiore Medical Center study entitled, “High Prevalence of High Grade Anal Intraepithelial Neoplasia in HIV-Infected Women Screened for Anal Cancer,” to be published in the Journal of Aids on May 1.

“Anal cancer was widely associated with HIV-infected men who have sex with men,” said Mark H. Einstein, MD, MS, Director of Clinical Research, Division of Gynecologic Oncology at Montefiore Medical Center and Professor at Albert Einstein College of Medicine. “But now, this study reveals anal precancerous disease in a high proportion of women with HIV.”

Out of 715 asymptomatic HIV-infected women studied, 10.5% exhibited some form of anal disease and approximately one third of them were found to be true pre-cancerous disease. The researchers determined that this is likely due to the fact that HIV promotes human papillomavirus (HPV) persistence and consequently, which is known to cause nearly all anal cancers. HIV-infected individuals are also at increased risk for the development of many other HPV-associated neoplasms.

The incidence of anal carcinoma (AC) has been increasing despite the implementation of antiretroviral therapy (ART), which has not been shown to consistently alter the course of HPV–associated anogenital disease.

The women studied were Montefiore patients in the Bronx, which has one of the highest HIV prevalence rates in the United States. Data indicates that 1.8% of the Bronx population is known to be HIV infected, representing 3% of the total number of HIV patients in the entire country. Montefiore is the largest provider of medical services for people with HIV in the Bronx and has adopted routine screening for AC with annual anal cytology in all HIV-infected patients.

As a result of these findings, Dr. Einstein and his colleagues recommend that all HIV+ women who have any abnormal anal cytology be referred for high resolution anoscopy, particularly those with poorly controlled HIV who are significantly at even higher risk for harboring a high-grade AIN than women who are well controlled. Also, all HIV infected men and women should be considered for anal cancer screening. Given the lower high-grade anal disease prevalence in women with well-controlled HIV, other strategies to improve disease ascertainment, such as inclusion of HPV testing might be found to be useful for AC screening. This risk stratification might prove to be different for women than it is for men, where prevalence rates seem to be considerably higher. Given the high rate of high-grade anal precancerous lesions in screened HIV-infected women and an aging population of HIV-infected patients, measures to increase routine AC screening should be strongly considered. Depending on the size of the pre-cancerous legion, it can be removed long before it becomes cancer, thus being able to save lives.

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